Fox William D, Higgins Brian, Maiese Krista M, Drobnjak Marija, Cordon-Cardo Carlos, Scher Howard I, Agus David B
Cedars-Sinai Prostate Cancer Center, Los Angeles, California 90048, USA.
Clin Cancer Res. 2002 Oct;8(10):3226-31.
Human tumors are dependent on angiogenesis for growth, and vascular endothelial growth factor (VEGF) is a major regulator of this process. We aimed to study clinical utility of a recombinant humanized monoclonal anti-VEGF antibody (rhu alpha VEGF) in the treatment of the CWR22R androgen-independent xenograft model of prostate cancer.
rhu alpha VEGF has previously shown clinical activity in several xenograft cancer models. We administered 5 mg/kg rhu alpha VEGF i.p. twice weekly as a single agent and together with paclitaxel to established CWR22R xenografts.
rhu alphaVEGF inhibited established tumor growth by 85% (P < 0.01 for trajectories of the average tumor volumes of the groups) at 3 weeks, but after cessation of rhu alpha VEGF treatment, tumor regrowth ensued. A paclitaxel dosage of 6.25 mg/kg s.c. five times/week slowed tumor growth (72% compared with controls at 3 weeks, P = 0.02). The combination of paclitaxel and rhu alpha VEGF resulted in greater inhibition of tumor growth than that observed with either agent alone (98% growth inhibition, P = 0.024 versus rhualpha VEGF alone and P = 0.02 versus paclitaxel alone). Paclitaxel alone had no antiangiogenic effects at the dosage studied, whereas rhu alpha VEGF had significant inhibition of angiogenesis, noted by microvessel density and CD34 staining.
rhu alpha VEGF has cytostatic clinical activity in this androgen-independent prostate cancer xenograft model, and the addition of paclitaxel demonstrates increased clinical activity.
人类肿瘤的生长依赖于血管生成，而血管内皮生长因子（VEGF）是这一过程的主要调节因子。我们旨在研究重组人源化单克隆抗VEGF抗体（rhuαVEGF）在治疗前列腺癌CWR22R雄激素非依赖性异种移植模型中的临床效用。
rhuαVEGF先前已在几种异种移植癌症模型中显示出临床活性。我们将5mg/kg的rhuαVEGF腹腔注射，每周两次，作为单一药物，并与紫杉醇联合应用于已建立的CWR22R异种移植瘤。
rhuαVEGF在3周时抑制已建立的肿瘤生长达85%（各组平均肿瘤体积轨迹的P<0.01），但在停止rhuαVEGF治疗后，肿瘤随之复发。6.25mg/kg的紫杉醇皮下注射，每周5次，减缓了肿瘤生长（3周时与对照组相比为72%，P=0.02）。紫杉醇和rhuαVEGF联合使用比单独使用任何一种药物对肿瘤生长的抑制作用更大（生长抑制率为98%，与单独使用rhuαVEGF相比P=0.024，与单独使用紫杉醇相比P=0.02）。在所研究的剂量下，单独使用紫杉醇没有抗血管生成作用，而rhuαVEGF对血管生成有显著抑制作用，这通过微血管密度和CD34染色得以体现。
rhuαVEGF在这种雄激素非依赖性前列腺癌异种移植模型中具有细胞生长抑制的临床活性，添加紫杉醇可增强临床活性。
